Background Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD. Methods Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2. Results Thirty-seven studies were included. Ten cardiac magnetic resonance studies reported MPRI and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 2.01 ± 0.41 in patients and from 1.50 ± 0.47 to 2.68 ± 0.49 in controls without CMD. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively. Conclusions This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. In current clinical practice, CMD is generally diagnosed with a CFR less than 2.0. However, due to heterogeneity in methodology and reporting of outcome measures, outcomes could not be compared and no definite reference values could be provided.

This study examines the way side effects information is presented in patient information leaflets about drugs. In a field experiment, we tested the effects of two attempts to improve a side effects paragraph in a leaflet about a nonsteroid anti-inflammatory drug. First, a short introductory passage on the nature of side effects was added. Second and more importantly, we changed the frequency descriptors (FDs) for the side effects. A preliminary study had shown that the frequencies associated with common Dutch FDs are much higher than the writers of patient information leaflets and package inserts mean to convey. In our experiment we replaced the original FDs by lower-assessed FDs. For instance, soms (sometimes) was replaced by zelden (seldomly). Replacing FDs led to lower recall for the side effects mentioned in the leaflet. It also decreased the number of side effects experienced. Contrary to our expectations, lower FDs did not significantly increase the confidence in the safety and effectiveness of the drug, nor did they increase therapy compliance; incompliance was extremely rare in our sample of patients. Adding an introductory passage on the nature of side effects lowered FD interpretations. It did not significantly affect any of the other dependent variables.

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